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We developed intramolecular carboxyamidations of alkyne‐tethered O‐acylhydroxamates followed by either thermally induced spontaneous or 4‐(dimethylamino)pyridine‐catalyzed O→O or O→N acyl group migration. Under iron‐catalyzed conditions, the carboxyamidation products were generated in high yield from both Z‐alkene and arene‐tethered substrates. DFT calculations indicate that the iron‐catalyzed carboxyamidation proceeds via a stepwise mechanism involving iron‐imidyl radical cyclization followed by intramolecular acyloxy transfer from the iron center to the alkenyl radical center to furnish the cis‐carboxyamidation product. Upon treatment with 4‐(dimethylamino)pyridine, the Z‐alkene‐tethered carboxyamidation products underwent selective O→O acyl migration to generate 2‐acyloxy‐5‐acyl pyrroles. Thermal O→N acyl migration occurs during carboxyamidation if the Z‐alkene linker contains an alkyl or an aryl substituent at the β‐position of the carbonyl group. On the other hand, the arene linker‐containing compounds selectively undergo O→N acyl migration to generate N‐acyl‐3‐acylisoindolinones, and the corresponding O→O acyl migration forming isoindole derivatives was not observed. [ABSTRACT FROM AUTHOR]

A single acyloxy group at C‐2 can control the outcome of nucleophilic substitution reactions of pyran‐derived acetals, but the extent of the neighboring‐group participation depends on a number of factors. We show here that neighboring‐group participation does not necessarily control the stereochemical outcome of acetal substitution reactions with weak nucleophiles. The 1,2‐trans selectivity increased with increasing reactivity of the incoming nucleophile. This trend suggests the intermediacy of both cis‐fused dioxolenium ions and oxocarbenium ions in the stereochemistry‐determining step. In addition, as the electron‐donating ability of the neighboring group decreased, the preference for the 1,2‐trans products increased. Computational studies show how the barriers for the ring‐opening reaction on the dioxolenium ions and the transition states to provide the oxocarbenium ions change with the electron‐donating capacity of the C‐2‐acyloxy group and the reactivity of the nucleophile. [ABSTRACT FROM AUTHOR]

Acyl group migration has been the subject of several studies. Such migration processes may cause problems during synthesis, isolation, and purification of different acyl‐bearing compounds, and have biological relevance, for example, in the metabolism of pharmaceuticals. Considering the recent evidence of acyl group migration being possible even over glycosidic bonds, it could be hypothesized to be involved also in the regulation of biological activity of natural polysaccharides in the host cells. Migrations are mostly observed in carbohydrates, typically having several hydroxyl groups near each other. Several studies have investigated the migration in a single or only a few different carbohydrate molecules, providing different suggestions for the mechanisms of migration, seldom supported by comprehensive computational investigations. In this concept article we discuss the recent progress on the mechanistic aspects of acyl group migration, with carbohydrates in particular focus. [ABSTRACT FROM AUTHOR]

Acyl group migration affects the synthesis, isolation, manipulation and purification of all acylated organic compounds containing free hydroxyl groups, in particular carbohydrates. While several isolated studies on the migration phenomenon in different buffers have been reported, comprehensive insights into the overall migration process in different monosaccharides under similar conditions have been lacking. Here, we have studied the acyl migration in different monosaccharides using five different acyl groups by a combination of experimental, kinetic and theoretical tools. The results show that the anomeric configuration in the monosaccharide has a major influence on the migration rate, together with the relative configurations of the other hydroxyl groups and the nature of the migrating acyl group. Full mechanistic model, based on computations, demonstrates that the acyl migration proceeds through an anionic stepwise mechanism with linear dependence on the [OH−] and the pKa of the hydroxyl group toward which the acyl group is migrating. [ABSTRACT FROM AUTHOR]

Efficient methods for the synthesis of fluorinated compounds have been intensively studied, recently. Development of practical fluorinating reagents is indispensable for this purpose. Herein, bench‐stable electrophilic fluorinating reagents were synthesized as N‐fluorobenzenesulfonimide (NFSI) substitutes. Reagents obtained by replacing one of the NFSI sulfonyl groups with an acyl group led to the highly selective monofluorination of silyl enol ethers with suppression of undesired overreaction, that is, difluorination. On the other hand, reagents bearing electron‐withdrawing substituents at NFSI benzenesulfonyl groups efficiently facilitated the difluorination of silyl enol ethers under base‐free conditions. Thus, both mono‐ and difluorinated target materials were prepared from the same substrate. [ABSTRACT FROM AUTHOR]

4‐Substitution on proline directly impacts protein main chain conformational preferences. The structural effects of N‐acyl substitution and of 4‐substitution were examined by NMR spectroscopy and X‐ray crystallography on minimal molecules with a proline 4S‐nitrobenzoate. The effects of N‐acyl substitution on conformation were attenuated in the 4S‐nitrobenzoate context, due to the minimal role of the n→π* interaction in stabilizing extended conformations. By X‐ray crystallography, an extended conformation was observed for most molecules. The formyl derivative adopted a δ conformation that is observed at the i+2 position of β‐turns. Computational analysis indicated that the structures observed crystallographically represent the inherent conformational preferences of 4S‐substituted prolines with electron‐withdrawing 4‐position substituents. The divergent conformational preferences of 4R‐ and 4S‐substituted prolines suggest their wider structure‐specific application in molecular design. In particular, the proline endo ring pucker favored by 4S‐substituted prolines uniquely promotes the δ conformation [(ϕ, ψ) ≈(−80°, 0°)] found in β‐turns. In contrast to other acyl capping groups, the pivaloyl group strongly promoted trans amide bond and polyproline II helix conformation, with a close n→π* interaction in the crystalline state, despite the endo ring pucker, suggesting its special capabilities in promoting compact conformations in ϕ due to its strongly electron‐donating character. [ABSTRACT FROM AUTHOR]

Abstract: A general efficient and site‐selective cobalt‐catalyzed insertion of isonitrile into C−H and N−H bonds of arylamides through C−H bond activation and alcohol assisted intramolecular trans‐amidation is demonstrated. This straightforward approach overcomes the limitation by the presence of strongly chelating groups. Isolation of CoIII‐isonitrile complex B has been achieved for the first time to understand the reaction mechanism. [ABSTRACT FROM AUTHOR]

A novel intramolecular oxycyanation of methylenecyclopropanes is reported that proceeds through oxidative cleavage of the N−CN bond and subsequent palladium transfer from N to O of the amide group. A range of substituted benzo[ d][1,3]oxazines with a cyano group are readily furnished by this newly developed oxycyanation reaction. Tris(4-trifluoromethylphenyl)phosphine as a ligand has been found to be crucial to effectively promote the transformation with high chemo- and regioselectivity. Moreover, the reaction outcome can be significantly affected by the electronic effect of the acyl group attached to the nitrogen atom of methylenecyclopropanes. When R3 is a chloromethyl group, the pyrrolo[2,3- b]quinoline derivative is obtained by thermal-induced [3+2] cycloaddition of methylenecyclopropane to the methanediimine intermediate. [ABSTRACT FROM AUTHOR]

The asymmetric Michael reaction between 5 H-oxazol-4-ones and α,β-unsaturated acyl imidazoles is reported. A novel 2-benzo[ b]thiophenyl-modified chiral ProPhenol species is synthesized and used as a ligand, leading to good enantioselectivities in this asymmetric conjugate addition reaction. Furthermore, the introduction of phenol additives as achiral co-ligands is found to improve the reaction's chemical yields, diastereoselectivities, and enantioselectivities. [ABSTRACT FROM AUTHOR]

Racemic 4- O-phenoxycarbonyl and 4- O-phenoxythiocarbonyl derivatives of myo-inositol orthoformate undergo thermal intramolecular cyclization in the solid state to yield the corresponding 4,6-bridged carbonates and thiocarbonates, respectively. The thermal cyclization also occurs in the solution and molten states, but less efficiently, suggesting that these cyclization reactions are aided by molecular pre-organization, although not strictly topochemically controlled. Crystal structures of two carbonates and a thiocarbonate clearly revealed that the relative orientation of the electrophile and the nucleophile in the crystal lattice facilitates the intramolecular cyclization reaction and forbids the intermolecular reaction. The correlation observed between the chemical reactivity and the non-covalent interactions in the crystal of the reactants provides a way to estimate the chemical stability of analogous molecules in the solid state. [ABSTRACT FROM AUTHOR]

A detailed computational and kinetic analysis of the acetylation of 1-phenylethanol with acetic anhydride catalyzed by planar chiral 4-(dimethylamino)pyridine (DMAP) catalyst (−)- 1 is presented. The study includes a computational investigation of the potential-energy surface including the acylation and stereoselective transition states at the DFT level of theory. Experimentally, the kinetic study shows that the reaction proceeds in a first-order manner in catalyst, whereas both substrates, acetic anhydride and 1-phenylethanol, show fractional order, which is in accordance with steady-state conditions. The fractional order depends on an equilibrium between the free catalyst and the acetylated catalyst. [ABSTRACT FROM AUTHOR]

An acyl-functionalized phosphasilene, LSi(CO tBu)P(SiMe3) (L=PhC(N tBu)2) was synthesized on a new route by the addition of tBuCOCl to the phosphinosilylene LSiP(SiMe3)2 and subsequent Me3SiCl elimination. DFT studies elucidated its molecular structure, the influence of the acyl group on UV/Vis transitions, and revealed the mechanism. The intermediate LSi(CO tBu)ClP(SiMe3)2, with a five-coordinate silicon center, was characterized by NMR spectroscopy and X-ray analysis. On the other hand, phosphasilene LSi(SiMe3)P(SiMe3) reacted with tBuCOCl by a [2+2] cycloaddition of the silicon-phosphorus double bond and the carbon-oxygen double bond in addition to Me3SiCl elimination, thereby affording the novel, fully characterized compound LSi(SiMe3)[PC( tBu)O] bearing a Si-P-C-O heterocycle with a phosphorus-carbon double bond. DFT studies suggest that two mechanisms occur simultaneously. [ABSTRACT FROM AUTHOR]

α,β-Unsaturated acyl cyanides are key bis-electrophile substrates for successful domino enantioselective organocatalyzed Michael-intramolecular acylation domino sequences. This new reactivity has been applied to the synthesis of enantioenriched azaspiro[4,5]decanone ring systems by a formal [3+3]spiroannulation, constituting a rare example of synthesis of glutarimides in an optically active form. [ABSTRACT FROM AUTHOR]

Cover Feature: 2-Sulfanylhydroquinone Dimer as a Switchable Fluorescent Dye (Chem. Eur. J. 62/2019) The monomesylated 2-sulfanyhydroquinone dimer emits blue light upon irradiation with UV light, whereas its photoluminescence activity turns off upon acylation of the phenolic hydroxyl group. 2-sulfanylhydroquinone dimer, acylation, biaryls, fluorescence, hydrolysis. [Extracted from the article]